Protein phosphatase 6 catalytic subunit (PPP6C)

Protein phosphatase 6 catalytic subunit (PPP6C) is a serine/threonine phosphatase from the phosphoprotein phosphatase (PPP) family that forms the enzymatic core of the PP6 holoenzyme, playing an essential role in regulating cell cycle progression, mitosis, DNA damage response, necroptosis, germ cell differentiation, and intracellular signal transduction. It specifically dephosphorylates key substrates such as Aurora A kinase, γ-H2AX, TAK1, and β-catenin. PPP6C is implicated in disease pathways such as cancer (notably colorectal cancer and melanoma with KRAS or BRAF mutations), inflammation, infertility, and immune dysfunction. Loss or mutation of PPP6C can drive drug resistance via activation of NF-κB and altered MAPK pathway responses, identifying it as a potential—but pharmacologically unexploited—therapeutic target with notable challenges for safety and cell specificity.

Other names

Serine/threonine-protein phosphatase 6 catalytic subunitPPP6PP6CPP6serine/threonine protein phosphatase catalytic subunitN-terminally processed PPP6C

For drugs (hypothetical or under study) that would affect PPP6C, mechanisms could include: Inhibition of phosphatase activity to modulate cell cycle or cell death pathways; Indirect action via co-targeting NF-κB or MAPK signaling pathways in PPP6C-deficient cancers.